The Symposia, 1933 — 2003

1982: Structures of DNA, Vol. XLVII

Organizer: James Watson

Francis Crick, in his autobiography, tells how Jim Watson was invited
to give a talk to the University of Cambridge Hardy Club. The talk
came after dinner of good food and wine, and "...when he came
to sum up he was quite overcome and at a loss for words. He gazed
at the model, slightly bleary-eyed. All he could manage to say was
'It's so beautiful, you see, so beautiful'". Some 30 years
later Watson wrote in the foreword to this Symposium volume that,
"...for a brief period it seemed by mere visual inspection
we must learn all its mysteries." In fact, it was understood
immediately that appreciating the visual beauty of DNA was not going
to suffice for understanding how DNA worked; for example, there
was the immediate problem of how the double helix unwound for replication,
a problem that much occupied Max Delbrück.

By 1982 the double helix was no less beautiful but it was no
longer so simple. Remarkably, Alex Rich had shown in 1979 that
a synthetic oligonucleotide could form a left-handed helix, Z-DNA.
Whether this existed in the cell was a different matter and Rich
opened the Symposium by reviewing the latest findings on possible
roles of Z-DNA in vivo. Other sessions dealt with methods for
analysis of the conformational dynamics of DNA molecules and chemical
modifications that altered DNA conformation. There was a fascinating
paper from Yanagida showing the behaviors of single DNA molecules
in solution. "It was a real treat" watching Yanagida's
videos, Aaron Klug wrote in his summary, "to those of us
who have been accustomed to seeing dead DNA molecules inert on
a [electron microscope] grid"

As in the earlier meetings on Chromatin (1977) and Chromosome
Structure and Function (1973), a good deal of the Symposium discussed

how DNA structure, interpreted rather broadly, was related to
DNA function. For example, there were sessions on DNA replication
and an extensive session on transcription. The latter included
an account by Walter Schaffner of the mysterious enhancers; he
had found the first—the SV40 72-bp repeat enhancer—the
year before. Another new area relating DNA structure (or at least
modification) to function was methylation, and here Adrian Bird,
Rudi Jaenisch, Barbara Migeon and Ahmed Bukhari, among others,
described the importance of the CpG sequence, although the term
"CpG island" does not seem to have yet come into use.

Klug remarked, "DNA sequencing is now so fast that it is
producing a staggering amount of data". He could not have
foreseen that there is staggering and staggering! Klug was impressed
by the 680,338 base pairs from 606 sequences were added to GenBank
in 1982; in 1992, 101,008,486 base pairs from 78,608 sequences,
while in 2001, a truly staggering 15,849,921,438 base pairs from
14,976,310 sequences were added! And this representing only sequences
in the public domain.